Single-Channel Characterization of a Nonselective Cation Channel from Human Placental Microvillous Membranes. Large Conductance, Multiplicity of Conductance States, and Inhibition by Lanthanides |
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Authors: | C. Grosman I.L. Reisin |
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Affiliation: | (1) Departamento de Química Analítica y Fisicoquímica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires (1113), Argentina, AR |
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Abstract: | The rate-limiting step for the maternofetal exchange of low molecular-weight solutes in humans is constituted by transport across a single epithelial layer (syncytiotrophoblast) of the placenta. Other than the well-established presence of a large-conductance, multisubstate Cl− channel, the ionic channels occurring in this syncytial tissue are, for the most part, unknown. We have found that fusion of apical plasma membrane-enriched vesicle fractions with planar lipid bilayers leads, mainly (96% of 353 reconstitutions), to the reconstitution of nonselective cation channels. Here we describe the properties of this novel placental conductance at the single-channel level. The channel has a large (>200 pS) and variable conductance, is cation selective (P Cl /P K ≅ 0.024), is reversibly inhibited (presumably blocked) by submillimolar La3+, has very unstable kinetics, and displays a large number (>10) of current sublevels with a ``promiscuous' connectivity pattern. The occurrence of both ``staircaselike' and ``all-or-nothing' transitions between the minimum and maximum current levels was intriguing, particularly considering the large number of conductance levels spanned at a time during the concerted current steps. Single-channel data simulated according to a multistate linear reaction scheme, with rate constants that can vary spontaneously in time, reproduce many aspects of the recorded subconductance behavior. The channel's sensitivity to lanthanides is reminiscent of stretch-sensitive channels which, in turn, suggests a physiological role for this ion channel as a mechanotransducer during syncytiotrophoblast-volume regulation. Received: 30 August 1999/Revised: 12 November 1999 |
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Keywords: | : Syncytiotrophoblast — Epithelia — Channel reconstitution — Substates — Mechanosensitivity |
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